Cardiovascular pathophysiology

Question 1

Explain the pathophysiology behind atherosclerosis.

Answer 1

• Dysfunctional endothelium due to RF.
• LDL pass from the lumen into tunica intima.
• Once here, they are oxidised. Causing the endothelium to express receptors, allowing monocytes to pass from the lumen into the intima.
• Here, monocytye = marcophage.
• Macrophage + oxidised LDL = ‘foam cell’
• Foam cells release chemokines into the lumen to attract more monocytes.
• When foam cells die, they release lipid promoting plaque growth.
• Foam cells also promote migration of SMC from the media into the intima and SMC proliferation.
• SMC proliferation increases collagen, hardening the plaque.
• Foam cells also release pro-inflammatory cytokines, attract neutrophils and reactive O2 species, increasing inflammation.
• When a plaque ruptures and release its contents into the lumen, a thrombus is formed which impedes blood flow

Question 2

What are the 2 complications of atherosclerosis?

Answer 2

• Plaque causes block in coronary artery. Reduces blood flow and hence O2 to myocardium. Especially in times of increased demand = Angina
• Plaque rupture = complete occlusion = MI

Question 3

Explain the blood supply to the heart

Answer 3

• RCA : supplys RA, RV inferior aspect of LV and posterior septal area
• RCA branches into :
• Circumflex : LA and posterior LV
• LAD : anterior LV and anterior septum

Question 4

what are the non modifiable RF for atherosclerosis ?

Answer 4

• Men
• Older age
• Family history

Question 5

What are the modifiable RF for atherosclerosis ?

Answer 5

• Smoking
• Raised cholesterol
• Obesity
• Poor diet and lack of exercise
• Excessive alcohol consumption
• Poor sleep
• Stress

Question 6

What medical co-morbidites increase the risk of atherosclerosis ?

Answer 6

• DM
• HTN
• CKD
• Inflammatory conditions (e.g. RA)
• Atypical antipsychotics

Question 7

Give 6 complications of atheroscleorisis

Answer 7

• Angina
• MI
• TIA
• Stroke
• Peripheral arterial disease
• Chronic mesenteric ischaemia

Question 8

What is the medication for primary prevention of CVD based on ?

Answer 8

• QRISK3 score - percentage risk of a pt having a stroke or myocardial infarction in the next 10 years

Question 9

When is someone offered medication for primary prevention of CVD and what is it ?

Answer 9

• QRISK3 >10%
• Atorvostatin 20mg

Question 10

What pts are offered 20mg atorvostatin for primary prevention of CVD despite QRISK score ?

Answer 10

• CKD (eGFR less than 60ml)
• T1DM for >10 years or are over 40 years

Question 11

What medications other than a statin can be used to lower cholesterol ?

Answer 11

• Ezetimibe -> inhibits cholesterol absorption in the intestine
• PCSk9 inhibitor (evolocumab, alirocumab) -> monoclonal antibodies, very specialised

Question 12

What is used in secondary prevention for CVD ?

Answer 12

4 A’s
- A : Antiplatelet
- A : Atorvostatin (80mg)
- A : Atenolol (or other BB)
- A : ACEI

Question 13

What is the genetic inheritance of familial hypercholesterolaemia

Answer 13

• Autosommal dominant

Question 14

What features of used for the diagnosis of familial hypercholesterolaemia

Answer 14

• Fx of premature CVD (MI <60 in 1st degree relative)
• Very high cholesterol (>7.5mmol in adult)
• Tendon zanthomata (hard nodules often on the hand and achilles